In acute isovolemic fetal anemia there is an increased blood flow to the brain and heart with no change in blood pressure or cardiac output. In contrast, in chronic isovolemic fetal anemia we have found increases in blood flow to all tissues except the placenta. Despite an increase in cardiac output, mean arterial pressure falls indicating a major decrease in systemic vascular resistance. In the proposed studies we plan to examine some of the mechanisms that determine vascular resistance, cardiac output and fluid balance in fetal adaptation to chronic anemia. Specifically, we will test the following hypotheses: (1) The mechanism of the decrease in vascular resistance is primarily related to the decrease in blood viscosity hindrance in chronically anemic fetuses in which the viscosity, but not oxygen content is acutely returned to normal by infusion of methemoglobin treated red blood cells. Secondarily, we will test the hypothesis that endothelial derived relaxant factor (EDRF) can account for the remaining decrease in vascular resistance in individual tissues with chronic anemia. (2) The increase in cardiac output occurs predominantly by an increase in stroke volume mediated by ventricular remodelling. By remodelling we mean an increase in end-diastolic volume and stroke volume as a function of filling pressure in control and chronically anemic fetuses. (3) As a result of a decrease in precapillary/postcapillary resistance, capillary hydrostatic pressure will increase and there will be a increase in a net capillary filtration and lymph flow. We will measure lymph flow and the extent of the increase in extravascular fluid by determining the sodium and inulin volume of distribution. We will use these measurements to further estimate the forces that determine fluid filtration.